Arzerra Seen as Alternative for Lupus Patients with Adverse Reactions to Rituxan

Reactions following Rituxan (rituximab) infusions often limit its repeat use in patients with severe systemic lupus erythematosus (SLE), and the alternative B-cell-depleting agent Arzerra (ofatumumab) may be a good option for these people, according to researchers at the Karolinska Institute.

Their study, “Ofatumumab treatment in lupus nephritis patients“, published in Clinical Kidney Journal, describes Arzerra’s positive results in four SLE patients who developed adverse reactions to Rituxan.

Rituxan treatment is being increasingly used in severe SLE patients, but it is often associated with the development of infections or with infusion-related reactions that limit its continued use in patients who exhibit an initial good response to treatment. It is thought that such infusion-related reactions may be caused by an immune response to the mouse component of Rituxan. The researchers assessed whether Rituxan therapy could be replaced by Arzerra, a fully humanized anti-CD20 antibody.

The authors report four patients from the Karolinska SLE cohort with refractory lupus nephritis, one of the most serious manifestations of SLE that affects the kidneys, who initially experienced beneficial effects of Rituxan but developed infusion reactions upon retreatment.

The first case was a 27-year old women who was first diagnosed with SLE at age 8. She received two rounds of Rituxan treatment at age 23, due to lupus nephritis class V that did not respond to mycophenolate mofetil (MMF). She experienced infusion reaction with fever and chills. Arzerra treatment was initiated seven months after the second course of Rituxan due to signs of active lupus nephritis (albumin protein in the urine), and was again administered 14 months after the first infusion. The patient now presents normal levels of albumin in her urine, 18 months after the last infusion.

The second case was a female patient, born in 1975, diagnosed with SLE at age 29. She received Rituxan for a lupus nephritis class IV-S, which induced disease remission for several years, but infusion reactions were observed upon disease relapse at age 36. The patient was then given Arzerra and had an initial response to treatment, but relapsed. Further doses of Arzerra were administered, but the patient developed urticaria and the treatment was not repeated.

A third case three involved a 46-year-old women diagnosed at age 25. She received cyclophosphamide and Rituxan due to nephirtis class IV/V at age 31, but developed chills, fever, hypertension, and tachycardia. Other treatments, such as corticosteroids, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers were used, but the patient relapsed and restarted Rituxan. Given that the patient developed infusion reactions, Arzerra was started and administered as a maintenance treatment every six months in a total of seven cycles. Her levels of albumin in the urine are normal three years after initiation of Arzerra.

In the fourth case, a women born in 1980 was diagnosed with SLE at age 27 years. As a result of lupus nephritis class V that did not respond to conventional therapy, she received Rituxan monotherapy at age 28. A second treatment of Rituxan and cyclophosphamide administered a year later induced infusion reactions, but the disease still remained in remission for the following three years. After a relapse, she was given Arzerra without adverse effects. Her urine albumin levels were normal one year after last treatment.

Together, these data suggest that SLE patients with lupus nephritis who had a good response to Rituxan but later exhibited infusion-related reactions may be effectively treated with Arzerra.

These two drugs are approved by the U.S. Food and Drug Administration for the treatment of certain leukemias and/or lymphomas, and Rituxan is also indicated for certain rheumatoid arthritis patients.  Neither is an approved SLE treatment, but Rituxan is allowed to be prescribed off-label for serious diseases like SLE.